Stability of CXCL-8 and related AU-rich mRNAs in the context of hepatitis C virus replication in vitro

J Infect Dis. 2006 Mar 15;193(6):802-11. doi: 10.1086/500510. Epub 2006 Feb 13.


Background: Previous studies have shown that levels of CXCL-8 are elevated in patients with chronic hepatitis C virus (HCV) infection and are highest in nonresponders to interferon (IFN) therapy and that CXCL-8 inhibits IFN antiviral action. CXCL-8 expression involves AU-rich elements (AREs) in 3' untranslated regions that regulate mRNA stability. CXCL-8 mRNA stability was, therefore, investigated in the context of HCV replication in 4 replicon cell lines, Huh7 and Huh7.5 cells, and primary human fetal hepatocytes.

Methods: The half-life of CXCL-8 mRNA was measured by use of real-time reverse-transcription polymerase chain reaction following tumor necrosis factor (TNF)- alpha induction in the presence and absence of inhibitors of transcription and translation. Cellular mRNAs containing AREs were assessed by custom microarray analyses.

Results: The half-life of CXCL-8 mRNA increased in 3 of 4 HCV replicon cell lines, particularly after treatment with TNF- alpha , a potent inducer of CXCL-8. CXCL-8 mRNA was superinduced by TNF- alpha in the presence of the protein-synthesis inhibitor cycloheximide. Analysis of >1500 ARE-containing cellular mRNAs, by use of microarrays, revealed that CXCL-8 and other newly identified ARE genes were induced by TNF- alpha in Huh7 cells and were coordinately regulated.

Conclusion: The data suggest that increased CXCL-8 gene expression in the context of HCV replication involves posttranscriptional events.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / metabolism
  • Cell Line
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Gene Expression / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Hepacivirus / physiology*
  • Humans
  • Interleukin-8
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • RNA Stability
  • RNA, Messenger / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Uridine / metabolism
  • Virus Replication*


  • CXCL8(3-73)K11R,G31P, bovine
  • Chemokines, CXC
  • Interleukin-8
  • Peptide Fragments
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Adenine
  • Uridine